Background The community-based, 4-level intervention of the European Alliance Against Depression (EAAD) is simultaneously addressing depression and suicidal behavior. Intervention activities target primary care health professionals (level 1), the general public (level 2), community facilitators (level 3), and patients and their relatives (level 4). Activities comprise the digital iFightDepression tool, a guided self-management tool based on cognitive behavioral therapy. Objective This study aimed to present the European Union–cofunded EAAD-Best study protocol, aiming at the implementation, dissemination, and evaluation of the 4-level intervention and the iFightDepression tool in several countries across Europe. Methods The 4-level intervention has been implemented for the first time in Bulgaria, Estonia, Greece, and Poland. In 3 countries that have already implemented the 4-level intervention (Hungary, Ireland, and Spain), activities have been extended to new regions. In addition, the nationwide uptake of the iFightDepression tool by patients with depression has been promoted in all mentioned countries and Italy. Results To evaluate the implementation of the 4-level intervention and the iFightDepression tool, data related to the process, output, and outcome were collected between 2022 and 2024. Data processing and analyses started in 2023. Analyses are expected to be completed in 2024. Results are expected to be published in 2025. Conclusions This paper informs researchers, practitioners, and stakeholders on how to implement best practices in mental health promotion and evaluate their effectiveness. International Registered Report Identifier (IRRID) DERR1-10.2196/64218